Extracellular purines serve as an innate trigger to allograft rejection (145.39)
| Autor: | Dawn Reichenbach, Qi Li, Anthony Demetris, Fadi Lakkis |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 184:145.39-145.39 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Innate immune triggers are well studied in infectious models, yet they remain unclear in solid organ transplantation. Extracellular purines (e.g. ATP, adenosine), which signal through receptors on immune cells, modulate the extent of ischemia reperfusion injury. To test the effect of purinergic signaling on graft rejection, we used a cardiac transplant model in outbred mice in which accelerated graft rejection occurs within 4 days post-transplantation and is highly dependent on innate mediators. Treatment with NECA, an adenosine receptor agonist, 2 hours prior to heterotopic heart transplantation (n=8) completely abrogated accelerated rejection compared to untreated outbred mice (incidence = 28%, n=35). CD39 and CD73 are ectoenzymes responsible for metabolism of extracellular ATP to adenosine. To determine the effect of increased extracellular ATP in the local graft environment, hearts from CD73-deficient B6 mice were transplanted to BALB/c recipients. Accelerated rejection occurred in 24% of grafts from CD73-/- mice (n=17) compared to 2% of grafts from wt inbred controls (n=42). Skin transplants from CD39-/- and CD73-/- mice to BALB/c mice (n=8/group) rejected at the same rate as wt control B6 to BALB/c skin transplants (n=8), suggesting the effect was restricted to vascularized transplants. Our data suggests that modulation of purine metabolism serves as an early trigger of the innate immune response in vascularized organ transplantation. |
| Databáze: | OpenAIRE |
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